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AIMS: Histology and retrospective clinical studies have indicated that the amount of neointimal hyperplasia is dependent on the arterial injury induced during stent implantation. This study analysed, prospectively, the impact of high vs low pressure stent implantation techniques using a second generation stent on intimal hyperplasia and follow-up lumen dimensions. METHODS AND RESULTS: Post-intervention and follow-up (mean[+/-SD] 5.5+/-1.3 months) angiographic and intravascular ultrasound studies were performed on 120 Multi-Link HP stents randomized to implantation at either low (8-10 atm) or high (16-20 atm) pressure. Intravascular ultrasound measurements of the external elastic membrane, stent, and lumen cross-sectional area were performed at 1 mm axial increments. Peri-stent plaque+media cross-sectional area (external elastic membrane-stent cross-sectional area, intimal hyperplasia cross-sectional area (stent-lumen cross-sectional area at follow-up), intimal hyperplasia thickness and peri-stent tissue growth cross-sectional area (Deltapersistent plaque+media cross-sectional area) were calculated. Intravascular ultrasound demonstrated a larger minimal lumen cross-sectional area post-intervention in the high pressure group (7.3+/-2.0 vs 6.2+/-1.8 mm(2), P<0.001, high vs low pressure group, respectively). At follow-up, the mean intimal hyperplasia cross-sectional area (1.7+/-0.9 vs 1.5+/-0.8 mm(2), P=0.708), the mean intimal hyperplasia thickness (0.16+/-0.12 vs 0.16+/-0.12 mm, P=0.818) and peri-stent tissue proliferation cross-sectional area were not greater in the high pressure group. Thus, the minimal lumen cross-sectional area at follow-up continued to be greater (5.5+/-2.0 vs 4.7+/-1.7 mm(2), P=0.038) in the high pressure group. CONCLUSIONS: High pressure stent implantation results in greater stent expansion even with the less rigid second generation Multi-Link stent. Larger lumen dimensions persist at follow-up, while intimal hyperplasia is not significantly greater after high pressure implantation compared to the low pressure technique.